1. Leena A. Nylander-French, Ph.D., CIH
11/3/00
Toxicology of the Skin
Leena A. Nylander-French, Ph.D., CIH
159 Rosenau Hall
Tel
Science that studies adverse skin effects and the substances that produce them
9/23/2018
Dermal Toxicology

2. Prevalence of Skin Disease
Leena A. Nylander-French, Ph.D., CIH
11/3/00
Prevalence of Skin Disease
Occupational skin diseases are the second most common types of occupational disease
45,000 reported cases of occupational skin disease in 2002
15% of all occupational diseases in the US
: occupational skin diseases increased by 26%, and 75% of workers with occupational skin disease developed a chronic skin disease
9/23/2018
Dermal Toxicology

3. Prevalence of Skin Disease
Leena A. Nylander-French, Ph.D., CIH
11/3/00
Prevalence of Skin Disease
Greatest number of occupational skin disease cases occur in the agricultural and manufacturing industries
Occupational skin diseases are believed to be severely underreported and the true rate may be many fold higher
Estimated total annual costs (including lost work days and loss of productivity) associated with occupational skin disease may reach $1 billion
9/23/2018
Dermal Toxicology

4. Leena A. Nylander-French, Ph.D., CIH
11/3/00
9/23/2018
Dermal Toxicology

5. Leena A. Nylander-French, Ph.D., CIH
11/3/00
9/23/2018
Dermal Toxicology

6. Leena A. Nylander-French, Ph.D., CIH
11/3/00
9/23/2018
Dermal Toxicology

7. Leena A. Nylander-French, Ph.D., CIH
11/3/00
9/23/2018
Dermal Toxicology

8. Leena A. Nylander-French, Ph.D., CIH
11/3/00
Acetone
600 µmol Ethyl Acrylate
1.25 µmol TPA
60 µmol TPGDA
9/23/2018
Dermal Toxicology

9. Leena A. Nylander-French, Ph.D., CIH
11/3/00
Introduction to:
Structure and function of the skin
Percutaneous absorption
Metabolism
Allergic contact dermatitis
9/23/2018
Dermal Toxicology

10. Functions of the Skin Environmental barrier Mechanical support
diffusion barrier
metabolic barrier
Mechanical support
Neurosensory reception
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11. Functions of the Skin
Physiologically, skin participates directly in thermal, metabolic, electrolyte, hormonal, and immune regulation
1. Temperature regulation
regulation of blood flow
hair and fur
sweating
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12. Functions of the Skin 2. Metabolism keratin collagen melanin lipid
carbohydrate
respiration
biotransformation
vitamin D
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13. Functions of the Skin
3. Apocrine/eccrine/sebaceous glandular secretion
4. Endocrine
5. Immunological affector and effector
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14. Structure of the Skin Dermal surface area 1.5-2 m2
Two major components, separated with a basement membrane
epidermis (outer layer)
dermis (underlying epidermis)
Epidermis
Dermis
Hypodermis
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15. Figure 1. The major structures of the skin
Mukhtar, H., Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.
9/23/2018

16. Figure 2. Diagram of a cross section of human skin
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17. Epidermis Stratified squamous epithelium
Keratinocytes the major cell type
> 90% of all cells
Programmed process of differentiation
Divided into several layers based on the state of keratinocyte differentiation
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18. 1.25 µmol TPA
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19. Figure 3. Structure of the epidermis
Mukhtar, H., Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.
9/23/2018

20. Figure 4. Schematic of the Stratum Corneum
Leena A. Nylander-French, Ph.D., CIH
11/3/00
Figure 4. Schematic of the Stratum Corneum
Mukhtar, H., Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.
9/23/2018
Dermal Toxicology

21. Cell Types in Epidermis
Keratinocytes
Merkel cells
type I mechanoreceptor (sensory reception)
Melanocytes
pigment-producing (melanin granules) cells that originate in the neural crest
Langerhan’s cells
bone marrow derived antigen presenting cells that are localized in the viable epidermis
9/23/2018

22. Dermis Largest fraction of the skin Provides structural strength
approximately 90%
Provides structural strength
high content of collagen and elastin
Nerve and vascular networks and appendages required to support the epidermis
9/23/2018

23. Figure 1. The major structures of the skin
Mukhtar, H., Pharmacology of the Skin. CRC Press, Inc., Boca Raton, FL.
9/23/2018

24. 1.25 µmol TPA
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25. 1. Papillary Layer Underlies the epidermis Fibroblasts
Major synthetic product is type III collagen
Organized into small fiber bundles that contrast with the larger type I collagen fiber bundles found in the reticular dermis
Collagenase activity
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26. 2. Reticular Layer Superficial to the hypodermis
Composed primarily of type I collagen; organized in large fibrillar bundles
Contains large, fully matured elastic bundles that extend between the collagen fiber bundles
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27. Cell Types in Dermis Fibroblast Macrophages Mast cells
phagocytize and neutralize foreign cells and chemicals
process and present antigen to immunocompetent lymphoid cells
Mast cells
respond to light, cold, acute trauma, vibration, and pressure
initiate chemotaxis or vasodilation
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28. Hypodermis
Layer of mesenchymally derived adipose cells that form the connective tissue layer of the reticular dermis
Innermost layer of the skin
Provides cushion between the external skin layers and the internal structures such as bone and muscle
Energy reserve
Allows for skin mobility and molds body contours
Insulates the body
9/23/2018